Konopljika

Vitex agnus castus L. Verbenaceae

engl. chaste tree, chastberry; fr. gattilier, agneau-caste, poivre des moines, poivre sauvage; njem. Mönchspfeffer, Keuschlamm

BOTANIČKI PODACI

Konopljika je mediteranski grm visine 1-2 metra dugačkih zašiljenih listova, a mirisni cvjetovi plavkaste boje su smješteni na izduženom cvatu grozdolikog izgleda.

OFICINALNI DIJELOVI BILJKE

Plod (ESCOP, Komisija E). Eterično ulje dobiva se i iz listova i cvjetova.

KEMIJSKI SASTAV (AKTIVNE TVARI)

Iridoidi i heterozidi iridoida (oko 1%): aukubozid, aukubozid-4-hidroksibenzoat, anguzid (0,01-0,4%). Diterpeni: rotundifuran (0,04-0,30%), viteksilakton (0,02-0,17%), 6β,7β-diacetoksi-13-hidroksi-labda-8,14-dien (0,02-0,1%). Flavonoidi (0,05-0,08%): 6-C-glukozil-luteolin, metil-esteri kvercetagenina i 6-hidroksikemferol poput 3,6,7,4'-tetrametiletera-kvercetagenin (kasticin) kojeg ima 0,02-0,21%, te manje količine 3,6,7-trimetil-etera-kvercetagenina (krisofenol-D), 3,6,7,4'-tetrametiletera-6-hidroksikemferola i 3,6,7-trimetileter-6-hidroksi-kemferola. Eterično ulje (0,15-1,8%) koje sadrži 2-44% sabinena, 4-35% 1,8-cineola, 1-23% α-pinena, 5-12% E-β-farnezena, 1-6% β-kariofilena te limonen, bornil-acetat i α-terpenil-acetat. Tanini, trigliceridi.

INDIKACIJE/DJELOVANJE

Predmenstrualni sindrom (PMS) uključujući i simptome mastodinije i mastalgije; problemi menstraulnog ciklusa (polimenoreja, oligomenoreja, amenoreja) (ESCOP, Komisija E).

Tradicionalno se koristi stoljećima kao snažan anafrodizijak (Dioskorid), odakle potječe i naziv vitex agnus castus (vitez čestitosti), te narodni nazivi koji ga vezuju uz svećenstvo (biskupski papar, poivre de moines, Mönchspfeffer). Koristi se i za liječenje ženkse nepolodnosti, te bolestima vezanima za prolatkin i hiperprolaktinemiju, ali paradoksalno i kao galaktogog.

Prošireni spektar djelovanja uključuje i menopauzalne tegobe, endometriom i leiomiome.

TIPOVI EKSTRAKATA

Tinkture ili suhi standardizirani ekstrakti. Infuzi i dekokti nisu oficinalni i nepodesni su zbog neugodnog okusa.

POSOLOGIJA

Pripravci koji odgovaraju dnevnoj dozi od 30-40mg suhe druge. Doza se može višestruko povećati, pogotovo kod PMS-a do ekvivalenta od 240mg dnevno (ESCOP, komisija E). To čini vrlo "rastezljivu" posologiju od 10-40 kapi tinkture dnevno (1:5 w/v 60-70% etanol).

U uobičajenoj primjeni 40 kapi tinkture 1-3x dnevno.

KONTRAINDIKACIJE

Nepoznate (ESCOP, Komisija E).

Spekulativne: PR+ karcinomi dojke zbog mogućeg djelovanja na progesteron.

INTERAKCIJE S LIJEKOVIMA

Nepoznate (ESCOP, Komisija E).

Oprez kod korištenja lijekova antagonista ili modulatora dopaminskog receptora, zbog djelovanja konopljike na dopaminergički sustav. To uključuje haloperidol, ali i droge poput kokaina i amfetamina.

Farmakodinamska interakcija u slučaju oralnih kontraceptiva, antiestrogene i hormonski nadomjesne terapije (spekulativna).

OSOBNA ISKUSTVENA PRAKSA

Konopljika pripada u jedan od stupova fitoterapije u hormonskim tegobama. Vrlo neobičan mehanizam djelovanja uključuje hormonsku kontrolu putem dopaminergičkog sustava, odnosno D2 receptora koji se uglavnom vezuju za diterpenske spojeve poput rotundifurana. Moguće je da biljka ostvaruje svoj učinak i na druge načine. Vrlo su kontradiktorni učinci na prolaktin - više znanstvenih radova govori u prilog djelovanja na hiperprolaktinemiju, no u ljudi ovo je djelovanje ovisno o dozi. Jedna studija objavljuje kako u ljudima niske doze smanjuju prolaktin, dok visoke doze blago povećavaju prolaktinemiju.

Konopljiku svrstavam među biljke koje vrlo često propisujem, vjerojatno i zbog učestalosti tegoba ali i njene djeltovornosti kao monoterapije. Statistički, to su najčešće menopauzalne tegobe, PMS, leimiomi. Jedan je od klasika za liječenje steriliteta u žena, ako je izazvan hormonskim tegobama i nije kompliciran drugim faktorima. Njena je prednost sigurnost u upotrebi: u praksi nisam susreo niti jednu neželjenu nuspojavu konopljike, pokazuje dobar patient compliance zbog jednostavnosti uzimanja (tinktura, uglavnom 2x dnevno) i prihvatljivog okusa. Najviše preferiram tinkturu konopljike, premda nisam protivnik suhih standardiziranih ekstrakata i njihovih formulacijskih oblika. Konopljika se uvijek daje na "duge staze", odnosno u periodima od 1-6 mjeseci, što sugerira i ESCOP, a to je i posve logično imajući na umu dugotrajnost liječenja hormonskih disbalansa u žena. Svatko ima svoj stil, pa mi nije prvi odabir kod PCOS-a (policističnih jajnika), ali ju vrlo često sugeriram zajedno s drugim biljnim klasicima za PCO (kadulja, muškatna kadulja, anis).

Posologija je vrlo bitna. Koristim tinkturu 1:5 w/v 70% etanol, a puni efekt se najčešće postiže dozom od 40 kapi 2x dnevno, što treba imati na umu jer se kod nas sugerira doza od 40 kapi 1x dnevno.

Gotovo je nevjerojatno da još prije nekoliko godina, ovaj stoljećima poznata ljekovita biljka nije u Hrvatskoj bila šire korištena. Tada se pojavilo nekoliko novih registriranih proizvoda s ovom biljkom, a njeno korištenje, na moje zadovoljstvo, raste. Što je vrlo bitno - nije skupa!

REFERENCE

Review/meta analize

Herbal treatments for alleviating premenstrual symptoms: a systematic review. Dante G, Facchinetti F. J Psychosom Obstet Gynaecol. 2011 Mar;32(1):42-51. Epub 2010 Dec 21.

Medicinal plants as alternative treatments for female sexual dysfunction: utopian vision or possible treatment in climacteric women? Mazaro-Costa R, Andersen ML, Hachul H, Tufik S. J Sex Med. 2010 Nov;7(11):3695-714. doi: 10.1111/j.1743-6109.2010.01987.x. Epub 2010 Aug 16.

Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints. van Die MD, Burger HG, Teede HJ, Bone KM. J Altern Complement Med. 2009 Aug;15(8):853-62.

Are changes of prolactin levels the effectors of vitex agnus castus beneficial effects on the pre-menstrual syndrome? Tamagno G. Maturitas. 2009 Aug 20;63(4):369. Epub 2009 Jul 25.

[The premenstrual syndrome: effectiveness of Vitex agnus castus]. Döll M. Med Monatsschr Pharm. 2009 May;32(5):186-91. Review.

Can Vitex Agnus Castus be Used for the Treatment of Mastalgia? What is the Current Evidence? Carmichael AR. Evid Based Complement Alternat Med. 2008 Sep;5(3):247-50.

Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation. Dugoua JJ, Seely D, Perri D, Koren G, Mills E. Can J Clin Pharmacol. 2008 Winter;15(1):e74-9. Epub 2008 Jan 18.

Chaste tree for premenstrual syndrome. An evolving therapy in the United States. Mancho P, Edwards QT. Adv Nurse Pract. 2005 May;13(5):43-4, 46.

Herbs commonly used by women: an evidence-based review. Tesch BJ. Am J Obstet Gynecol. 2003 May;188(5 Suppl):S44-55. Review.

Vitex agnus castus essential oil and menopausal balance: a research update [Complementary Therapies in Nursing and Midwifery 8 (2003) 148-154]. Chopin Lucks B. Complement Ther Nurs Midwifery. 2003 Aug;9(3):157-60.

Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications. Wuttke W, Jarry H, Christoffel V, Spengler B, Seidlová-Wuttke D. Phytomedicine. 2003 May;10(4):348-57.

Herbs commonly used by women: an evidence-based review. Tesch BJ. Dis Mon. 2002 Oct;48(10):671-96. Review.

[Effectiveness of Vitex agnus-castus preparations]. Gorkow C, Wuttke W, März RW. Wien Med Wochenschr. 2002;152(15-16):364-72.

Is an extract of the fruit of agnus castus (chaste tree or chasteberry) effective for prevention of symptoms of premenstrual syndrome (PMS)? Huddleston M, Jackson EA. J Fam Pract. 2001 Apr;50(4):298.

Kliničke studije

Evaluating therapeutic effect in symptoms of moderate-to-severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Ma L, Lin S, Chen R, Zhang Y, Chen F, Wang X. Aust N Z J Obstet Gynaecol. 2010 Apr;50(2):189-93.

Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Ma L, Lin S, Chen R, Wang X. Gynecol Endocrinol. 2010 Aug;26(8):612-6.

Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis. van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ. J Altern Complement Med. 2009 Sep;15(9):1045-8.

Treatment for premenstrual syndrome with Vitex agnus castus: A prospective, randomized, multi-center placebo controlled study in China. He Z, Chen R, Zhou Y, Geng L, Zhang Z, Chen S, Yao Y, Lu J, Lin S. Maturitas. 2009 May 20;63(1):99-103. Epub 2009 Mar 9.

Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial. van Die MD, Burger HG, Bone KM, Cohen MM, Teede HJ. Menopause. 2009 Jan-Feb;16(1):156-63.

Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Rotem C, Kaplan B. Gynecol Endocrinol. 2007 Feb;23(2):117-22.

Double-blind, placebo-controlled study of Fertilityblend: a nutritional supplement for improving fertility in women. Westphal LM, Polan ML, Trant AS. Clin Exp Obstet Gynecol. 2006;33(4):205-8.

Extract of the seeds of the plant Vitex agnus castus proven to be highly efficacious as a repellent against ticks, fleas, mosquitoes and biting flies. Mehlhorn H, Schmahl G, Schmidt J. Parasitol Res. 2005 Mar;95(5):363-5. Epub 2005 Jan 29.

Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study. Halaska M, Beles P, Gorkow C, Sieder C. Breast. 1999 Aug;8(4):175-81.

Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Atmaca M, Kumru S, Tezcan E. Hum Psychopharmacol. 2003 Apr;18(3):191-5.

Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. Schellenberg R. BMJ. 2001 Jan 20;322(7279):134-7.

Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Berger D, Schaffner W, Schrader E, Meier B, Brattström A. Arch Gynecol Obstet. 2000 Nov;264(3):150-3.

[The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study]. Bergmann J, Luft B, Boehmann S, Runnebaum B, Gerhard I. Forsch Komplementarmed Klass Naturheilkd. 2000 Aug;7(4):190-9.

[Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: Results of a placebo-controlled double-blind study. Breast 1999;8:175-181]. Tschudin S, Huber R. Forsch Komplementarmed Klass Naturheilkd. 2000 Jun;7(3):162-4.

Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. Loch EG, Selle H, Boblitz N. J Womens Health Gend Based Med. 2000 Apr;9(3):315-20.

[Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo]. Halaska M, Raus K, Bĕles P, Martan A, Paithner KG. Ceska Gynekol. 1998 Oct;63(5):388-92.

[Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study]. Milewicz A, Gejdel E, Sworen H, Sienkiewicz K, Jedrzejak J, Teucher T, Schmitz H. Arzneimittelforschung. 1993 Jul;43(7):752-6.

[Amenorrhea. Favorable effect of Agnus castus (Agnolyt) on amenorrhea]. Amann W. ZFA (Stuttgart). 1982 Feb 10;58(4):228-31. German.

Predkliničke studije

Inhibitory effects of casticin on migration of eosinophil and expression of chemokines and adhesion molecules in A549 lung epithelial cells via NF-κB inactivation. Koh DJ, Ahn HS, Chung HS, Lee H, Kim Y, Lee JY, Kim DG, Hong M, Shin M, Bae H. J Ethnopharmacol. 2011 Jan 18.

Anti-inflammatory and enzyme inhibitory activities of a crude extract and a pterocarpan isolated from the aerial parts of Vitex agnus-castus. Ahmad B, Azam S, Bashir S, Khan I, Adhikari A, Choudhary MI. Biotechnol J. 2010 Nov;5(11):1207-15.

Opioidergic mechanisms underlying the actions of Vitex agnus-castus L. Webster DE, He Y, Chen SN, Pauli GF, Farnsworth NR, Wang ZJ. Biochem Pharmacol. 2011 Jan 1;81(1):170-7. Epub 2010 Sep 18.

Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus. Choudhary MI; Azizuddin, Jalil S, Nawaz SA, Khan KM, Tareen RB; Atta-ur-Rahman. Phytother Res. 2009 Sep;23(9):1336-9.

Vitex agnus castus as prophylaxis for osteopenia after orchidectomy in rats compared with estradiol and testosterone supplementation. Sehmisch S, Boeckhoff J, Wille J, Seidlova-Wuttke D, Rack T, Tezval M, Wuttke W, Stuermer KM, Stuermer EK. Phytother Res. 2009 Jun;23(6):851-8.

The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats. Saberi M, Rezvanizadeh A, Bakhtiarian A. Neurosci Lett. 2008 Aug 22;441(2):193-6. Epub 2008 Jun 18.

The effects of phytoestrogens on fracture healing: experimental research in New Zealand white rabbits. Oztürk A, Ilman AA, Sağlam H, Yalçinkaya U, Aykut S, Akgöz S, Ozkan Y, Yanik K, Kivçak B, Yalçin N, Ozdemir RM. Ulus Travma Acil Cerrahi Derg. 2008 Jan;14(1):21-7.

Estrogen-like activities in Vitex species from China determined by a cell based proliferation assay. Hu Y, Zhang QY, Hou TT, Xin HL, Zheng HC, Rahman K, Qin LP. Pharmazie. 2007 Nov;62(11):872-5.

The effects of Vitex agnus castus extract and its interaction with dopaminergic system on LH and testosterone in male mice. Nasri S, Oryan S, Rohani AH, Amin GR. Pak J Biol Sci. 2007 Jul 15;10(14):2300-7.

Anti-inflammatory and neuroprotective effect of a phytoestrogen compound on rat microglia. Marotta F, Mao GS, Liu T, Chui DH, Lorenzetti A, Xiao Y, Marandola P. Ann N Y Acad Sci. 2006 Nov;1089:276-81.

Activation of the mu-opiate receptor by Vitex agnus-castus methanol extracts: implication for its use in PMS. Webster DE, Lu J, Chen SN, Farnsworth NR, Wang ZJ. J Ethnopharmacol. 2006 Jun 30;106(2):216-21. Epub 2006 Jan 24.

A Vitex agnus-castus extract inhibits cell growth and induces apoptosis in prostate epithelial cell lines. Weisskopf M, Schaffner W, Jundt G, Sulser T, Wyler S, Tullberg-Reinert H. Planta Med. 2005 Oct;71(10):910-6.

Human gastric signet ring carcinoma (KATO-III) cell apoptosis induced by Vitex agnus-castus fruit extract through intracellular oxidative stress. Ohyama K, Akaike T, Imai M, Toyoda H, Hirobe C, Bessho T. Int J Biochem Cell Biol. 2005 Jul;37(7):1496-510.

Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). Liu J, Burdette JE, Sun Y, Deng S, Schlecht SM, Zheng W, Nikolic D, Mahady G, van Breemen RB, Fong HH, Pezzuto JM, Bolton JL, Farnsworth NR. Phytomedicine. 2004 Jan;11(1):18-23.

Antitumor activity of herbal supplements in human prostate cancer xenografts implanted in immunodeficient mice. Ng SS, Figg WD. Anticancer Res. 2003 Sep-Oct;23(5A):3585-90.

Evidence for estrogen receptor beta-selective activity of Vitex agnus-castus and isolated flavones. Jarry H, Spengler B, Porzel A, Schmidt J, Wuttke W, Christoffel V. Planta Med. 2003 Oct;69(10):945-7.

Cytotoxicity and apoptotic inducibility of Vitex agnus-castus fruit extract in cultured human normal and cancer cells and effect on growth. Ohyama K, Akaike T, Hirobe C, Yamakawa T. Biol Pharm Bull. 2003 Jan;26(1):10-8.

Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL. J Agric Food Chem. 2001 May;49(5):2472-9.

Pharmacological activities of Vitex agnus-castus extracts in vitro. Meier B, Berger D, Hoberg E, Sticher O, Schaffner W. Phytomedicine. 2000 Oct;7(5):373-81.

Growth inhibition of human breast cancer cells by herbs and phytoestrogens. Dixon-Shanies D, Shaikh N. Oncol Rep. 1999 Nov-Dec;6(6):1383-7.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells. Sliutz G, Speiser P, Schultz AM, Spona J, Zeillinger R. Horm Metab Res. 1993 May;25(5):253-5.

Toksičnost i interakcije

Vitex agnus castus: a systematic review of adverse events. Daniele C, Thompson Coon J, Pittler MH, Ernst E. Drug Saf. 2005;28(4):319-32. Review.

The Effects of Commercial Preparations of Herbal Supplements Commonly Used by Women on the Biotransformation of Fluorogenic Substrates by Human Cytochromes P450. Ho SH, Singh M, Holloway AC, Crankshaw DJ. Phytother Res. 2011 Jan 7. doi: 10.1002/ptr.3371.

Mutagenicity and antimutagenicity of teas used in popular medicine in the salmonella/microsome assay. Horn RC, Vargas VM. Toxicol In Vitro. 2008 Jun;22(4):1043-9. Epub 2007 Dec 31.

A prolactinoma masked by a herbal remedy. Gallagher J, Lynch FW, Barragry J. Eur J Obstet Gynecol Reprod Biol. 2008 Apr;137(2):257-8. Epub 2007 Feb 12.

Vitex agnus castus: a systematic review of adverse events. Daniele C, Thompson Coon J, Pittler MH, Ernst E. Drug Saf. 2005;28(4):319-32. Review.